When keratinocytes are exposed to DNA damaging elements (mutagens) such as ultraviolet (UV) radiation, cell cycle checkpoints are activated thereby blocking cell division. The arrest of the cell cycle in G2 phase after mutagen-induced damage allows time for DNA repair. However, if the checkpoint process is interrupted or inhibited, then the frequency of cancer-producing events (e.g., DNA mutations) is reduced. This has been demonstrated in vitro and in vivo through the application of caffeine to skin before and after UV irradiation (Lu et al., 2008, Cancer Res. 68:2523-2529; Heffernan et al., 2009, J. Invest. Dermatol. 129:1805-1815). The basis for this phenomenon is that caffeine inhibits the mitotic checkpoint pathway, allowing DNA-damaged cells to proceed to mitosis and die via apoptosis as their DNA is incapable of satisfactory replication. Allowing cell cycle progression despite DNA mutation/damage and the apoptotic cell death that occurs as a result prevents the fixation of mutagen-induced mutations in the affected tissue. This process thereby reduces the number of genetically altered cells that would otherwise have the potential to develop into cancerous lesions such as carcinoma.
The ability of caffeine to reduce the carcinogenic effects of UV light on skin has raised an interest in using this agent in skin care therapeutic and cosmetic skin care applications. However, the use of caffeine in skin care products is problematic given its lack of specificity. Aside from its salutary effects, caffeine can induce undesirable effects in skin (e.g., vasodilation, drying, etc.). Given these drawbacks, other approaches have been sought after for preventing the damaging effects of mutagens in skin and related tissues.
The use of short peptides for the development of skin care products is very popular due to their natural amino acid-based structure, specificity, lack of toxicity, and lack of side effects. These qualities render peptides as a suitable starting point for the development of novel chemopreventive agents for supplementation to skin care compositions. Peptides having chemopreventive and chemotherapeutic properties and that are applicable to protecting skin from the damaging effects of sunlight are described herein.